Wilms’ Tumor 1 (WT1) mRNA is a non-specific marker of measurable residual disease in acute myeloid leukemia (AML). Few studies have focused on the prognostic value of WT1 mRNA after initial remission induction of patients with AML who have received transplant treatments. Thus, we retrospectively analyzed the clinical features and prognostic impact of WT1 mRNA reduction in patients with AML after initial remission induction at our hospital. We classified the reduction in WT1 mRNA levels using logarithmic stratification, with particular focus on the prognostic impact of a 3-log reduction after initial remission induction. This single-center, retrospective, observational study included 71 consecutive patients with AML who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) between April 2013 and June 2023 and had WT1 mRNA quantified. Patients were grouped based on whether a 3-log reduction was observed during follow-up (N=30) or not (N=41). Among patients who did not achieve a 3-log reduction, European Leukemia Net (ELN) 2022 adverse risk was more common, and fewer patients showed complete hematological responses at transplantation. Patients who reached a 3-log reduction in WT1 mRNA after the initial remission induction had significantly longer overall survival (OS) and progression-free survival (PFS) and a lower relapse rate than patients who had not reached a 3-log reduction (2-year OS: 79.7% vs. 27.5%, 2-year PFS: 83.1% vs. 11.7% and 2-year cumulative relapse rate: 5.9% vs. 81.2%). In multivariate analysis, a 3-log reduction in WT1 mRNA after initial remission induction and ELN 2022 adverse risk by genetics were significantly associated with OS and PFS. We identified that patients with AML undergoing HSCT with an early and deep 3-log reduction in WT1 mRNA after initial remission induction were associated with low relapse rates and better long-term prognosis. Our data highlight the importance of WT1 mRNA reduction after initial remission induction.
背景：Wilms' Tumor (WT1) mRNA是急性髓性白血病（AML）中可测量的残留疾病的非特异性标志物。很少有研究关注接受移植治疗的AML患者初始缓解诱导后WT1 mRNA的预后价值。目的：因此，我们回顾性分析我院AML患者初始缓解诱导后WT1 mRNA降低的临床特征及对预后的影响。我们使用对数分层对WT1 mRNA水平的降低进行分类，特别关注初始缓解诱导后3对数降低对预后的影响。研究设计：这项单中心、回顾性、观察性研究纳入了71例在2013年4月至2023年6月期间接受同种异体造血干细胞移植（alloo - hsct）的AML患者，并对WT1 mRNA进行了量化。结果：根据随访中是否观察到3对数下降（N=30） （N=41）对患者进行分组。在未达到3 log降低的患者中，欧洲白血病网（ELN） 2022不良风险更常见，移植时出现完全血液学反应的患者更少。在初始缓解诱导后，WT1 mRNA达到3对数降低的患者与未达到3对数降低的患者相比，总生存期（OS）和无进展生存期（PFS）明显更长，复发率更低（2年OS: 79.7% vs. 27.5%， 2年PFS: 83.1% vs. 11.7%， 2年累积复发率：5.9% vs. 81.2%）。在多变量分析中，初始缓解诱导后WT1 mRNA的3对数降低和遗传导致的ELN 2022不良风险与OS和PFS显著相关。结论：我们发现接受HSCT的AML患者在初始缓解诱导后WT1 mRNA早期和深度3-log降低与低复发率和更好的长期预后相关。我们的数据强调了初始缓解诱导后WT1 mRNA减少的重要性。
{"title":"Clinical Outcomes of Early WT1 mRNA Reduction After Remission Induction in Newly Diagnosed Acute Myeloid Leukemia Undergoing Allogeneic Hematopoietic Stem Cell Transplantation","authors":"Takafumi Tsushima, Chiharu Kimeda, Natsumi Yoda, Kosuke Matsuo, Kazusuke Tanaka, Yasuhito Hatanaka, Rena Matsumoto, Sonoko Shimoji, Yoshikazu Utsu, Shin-Ichi Masuda, Nobuyuki Aotsuka","doi":"10.1016/j.jtct.2024.12.007","DOIUrl":"10.1016/j.jtct.2024.12.007","url":null,"abstract":"<div><div><em>Wilms’ Tumor 1 (WT1)</em> mRNA is a non-specific marker of measurable residual disease in acute myeloid leukemia (AML). Few studies have focused on the prognostic value of <em>WT1</em> mRNA after initial remission induction of patients with AML who have received transplant treatments. Thus, we retrospectively analyzed the clinical features and prognostic impact of <em>WT1</em> mRNA reduction in patients with AML after initial remission induction at our hospital. We classified the reduction in <em>WT1</em> mRNA levels using logarithmic stratification, with particular focus on the prognostic impact of a 3-log reduction after initial remission induction. This single-center, retrospective, observational study included 71 consecutive patients with AML who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) between April 2013 and June 2023 and had <em>WT1</em> mRNA quantified. Patients were grouped based on whether a 3-log reduction was observed during follow-up (N=30) or not (N=41). Among patients who did not achieve a 3-log reduction, European Leukemia Net (ELN) 2022 adverse risk was more common, and fewer patients showed complete hematological responses at transplantation. Patients who reached a 3-log reduction in <em>WT1</em> mRNA after the initial remission induction had significantly longer overall survival (OS) and progression-free survival (PFS) and a lower relapse rate than patients who had not reached a 3-log reduction (2-year OS: 79.7% vs. 27.5%, 2-year PFS: 83.1% vs. 11.7% and 2-year cumulative relapse rate: 5.9% vs. 81.2%). In multivariate analysis, a 3-log reduction in <em>WT1</em> mRNA after initial remission induction and ELN 2022 adverse risk by genetics were significantly associated with OS and PFS. We identified that patients with AML undergoing HSCT with an early and deep 3-log reduction in <em>WT1</em> mRNA after initial remission induction were associated with low relapse rates and better long-term prognosis. Our data highlight the importance of <em>WT1</em> mRNA reduction after initial remission induction.</div></div>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"31 3","pages":"Pages 168.e1-168.e12"},"PeriodicalIF":3.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142855577","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-01DOI: 10.1016/S2666-6367(25)01015-2
{"title":"Masthead (Purpose and Scope)","authors":"","doi":"10.1016/S2666-6367(25)01015-2","DOIUrl":"10.1016/S2666-6367(25)01015-2","url":null,"abstract":"","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"31 3","pages":"Page A1"},"PeriodicalIF":3.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143610669","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-01DOI: 10.1016/j.jtct.2024.12.020
Aasha I. Hoogland , Xiaoyin Li , Karnav Modi , Taylor Welniak , Yvelise Rodriguez , Nathaly Irizarry-Arroyo , Laura B. Oswald , Julia T. Snider , Sally W. Wade , Julio Chavez , Salvatore Corallo , Margaret Booth-Jones , Michael D. Jain , Frederick L. Locke , Heather S.L. Jim
<div><div>Axicabtagene ciloleucel (axi-cel), a chimeric antigen receptor T-cell therapy, has significantly improved clinical outcomes in adult patients with relapsed/refractory large B-cell lymphoma. However, few studies have examined patient-reported outcomes (PROs) or neurocognitive performance in patients treated with axi-cel. Moreover, no longitudinal PRO study has reported on patients treated with axi-cel as standard of care in the United States, to our knowledge. This paper reports on real-world changes in PROs (i.e., quality of life [QOL] and perceived cognition) and objective neurocognitive performance before treatment with axi-cel and in the first year after. Patients scheduled to receive axi-cel as standard of care were recruited from a single cancer center between March 2020 and June 2022. QOL was assessed using the EORTC QLQ-C30 and EQ-5D-5L at baseline recruitment (ie, prior to conditioning chemotherapy before axi-cel), and at 7, 14, 30, 60, 90, 180, and 360 days after receiving axi-cel. Perceived cognition was assessed using the Patient-Reported Outcomes Measurement Information System Cognitive Function 4a scale. Objective neurocognitive performance was assessed using a battery of tests at baseline, and 30, 90, and 360 days after receiving axi-cel. Random-effects mixed models evaluated changes in QOL, perceived cognition, and neurocognitive performance using all available data. Clinically meaningful change in QOL was defined as a difference of 10 points on the EORTC QLQ-C30. Clinically meaningful change in perceived cognition or neurocognitive performance was defined as a difference of 5 points. On average, participants (<em>N</em> = 53) were 63 years of age (SD = 13), and predominantly male (62%), White (92%), and college graduates (60%). Participants reported statistically significant improvements from baseline to day 360 in overall QOL, physical functioning, role functioning, and social functioning (<em>P</em>s < .05) after axi-cel, despite clinically significant worsening in the first 14 days. For role functioning and social functioning, improvements also met criteria for clinical significance. There were no statistically (<em>P</em>s > .05) or clinically significant changes in perceived cognition over time. Despite some transient declines, neurocognitive performance generally returned to or exceeded baseline levels by day 360 (<em>P</em>s < .01). However, visuospatial ability worsened by day 90 and did not recover to baseline levels by day 360 (<em>P</em> < .0001). These real-world data suggest that axi-cel is associated with significant improvements in overall QOL in the first year after infusion. These data are generally consistent with, or exceed, improvements in QOL reported from clinical trials of axi-cel therapy. Despite transient worsening in the acute period after treatment, neurocognitive performance in most domains also recovered to pretreatment levels by 1 year after infusion. These findings extend previo
{"title":"Real-World Patient-Reported and Neurocognitive Outcomes in the Year After Axicabtagene Ciloleucel","authors":"Aasha I. Hoogland , Xiaoyin Li , Karnav Modi , Taylor Welniak , Yvelise Rodriguez , Nathaly Irizarry-Arroyo , Laura B. Oswald , Julia T. Snider , Sally W. Wade , Julio Chavez , Salvatore Corallo , Margaret Booth-Jones , Michael D. Jain , Frederick L. Locke , Heather S.L. Jim","doi":"10.1016/j.jtct.2024.12.020","DOIUrl":"10.1016/j.jtct.2024.12.020","url":null,"abstract":"<div><div>Axicabtagene ciloleucel (axi-cel), a chimeric antigen receptor T-cell therapy, has significantly improved clinical outcomes in adult patients with relapsed/refractory large B-cell lymphoma. However, few studies have examined patient-reported outcomes (PROs) or neurocognitive performance in patients treated with axi-cel. Moreover, no longitudinal PRO study has reported on patients treated with axi-cel as standard of care in the United States, to our knowledge. This paper reports on real-world changes in PROs (i.e., quality of life [QOL] and perceived cognition) and objective neurocognitive performance before treatment with axi-cel and in the first year after. Patients scheduled to receive axi-cel as standard of care were recruited from a single cancer center between March 2020 and June 2022. QOL was assessed using the EORTC QLQ-C30 and EQ-5D-5L at baseline recruitment (ie, prior to conditioning chemotherapy before axi-cel), and at 7, 14, 30, 60, 90, 180, and 360 days after receiving axi-cel. Perceived cognition was assessed using the Patient-Reported Outcomes Measurement Information System Cognitive Function 4a scale. Objective neurocognitive performance was assessed using a battery of tests at baseline, and 30, 90, and 360 days after receiving axi-cel. Random-effects mixed models evaluated changes in QOL, perceived cognition, and neurocognitive performance using all available data. Clinically meaningful change in QOL was defined as a difference of 10 points on the EORTC QLQ-C30. Clinically meaningful change in perceived cognition or neurocognitive performance was defined as a difference of 5 points. On average, participants (<em>N</em> = 53) were 63 years of age (SD = 13), and predominantly male (62%), White (92%), and college graduates (60%). Participants reported statistically significant improvements from baseline to day 360 in overall QOL, physical functioning, role functioning, and social functioning (<em>P</em>s < .05) after axi-cel, despite clinically significant worsening in the first 14 days. For role functioning and social functioning, improvements also met criteria for clinical significance. There were no statistically (<em>P</em>s > .05) or clinically significant changes in perceived cognition over time. Despite some transient declines, neurocognitive performance generally returned to or exceeded baseline levels by day 360 (<em>P</em>s < .01). However, visuospatial ability worsened by day 90 and did not recover to baseline levels by day 360 (<em>P</em> < .0001). These real-world data suggest that axi-cel is associated with significant improvements in overall QOL in the first year after infusion. These data are generally consistent with, or exceed, improvements in QOL reported from clinical trials of axi-cel therapy. Despite transient worsening in the acute period after treatment, neurocognitive performance in most domains also recovered to pretreatment levels by 1 year after infusion. These findings extend previo","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"31 3","pages":"Pages 157.e1-157.e13"},"PeriodicalIF":3.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142903470","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-01DOI: 10.1016/j.jtct.2024.12.022
Moazzam Shahzad , Qamar Iqbal , Muhammad Kashif Amin , Amir Kasaiean , Iman Menbari Oskouie , Sarmad Zaman Warraich , James Yu , Iqra Anwar , Michael Jaglal , Muhammad Umair Mushtaq
Allogeneic hematopoietic cell transplantation (allo-HCT) is a potential cure for many hematological malignancies. Historically, older adults were not considered eligible for allo-HCT due to increased toxicity and mortality concerns. This systematic review and meta-analysis aim to explore the outcomes of allo-HCT in patients aged 70 years or older. Following Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines, a comprehensive literature search was performed on PubMed, Cochrane Register of Controlled Trials, and Clinicaltrials.gov using MeSH terms and keywords for “Hematopoietic Stem Cell Transplantation” AND “Outcome Assessment” from the date of inception to June 30, 2024. Our search produced 102 articles. After excluding irrelevant and review articles during primary and secondary screening, eight original studies reporting outcomes of allo-HCT in patients aged 70 years or older were included. The survival data were retrieved from Kaplan–Meier (KM) curves using an online plot digitizer tool to calculate the overall survival (OS) and disease-free survival (DFS). The pooled KM curves were plotted and analyzed using the “MetaSurvival” package of R software version 4.2.1. Proportions and 95% confidence intervals (CIs) were extracted as well. A total of 2519 patients aged 70 years or older with allo-HCT were included in the analysis. The included patients’ age ranged from 70 to 84 years, and 68% were male. Median follow-up was 23.2 (0.4 to 122.5) months. The combined median OS was 14.84 months (95% CI: 11.61 to 19.50), with OS rates at 6, 12, 24, and 36 months of 71.8%, 54.5%, 41.9%, and 34.9%, respectively. The estimated pooled mean OS was 28.62 months (95% CI: 23.41 to 31.44). The pooled median DFS was 10.54 months (95% CI: 7.93 to 14.17), with DFS rates at 6, 12, 24, and 36 months of 61.5%, 47.5%, 37%, and 30.6%, respectively. The estimated pooled mean DFS was 24.45 months (95% CI: 18.30 to 23.74). The relapse rate ranged from 28% to 55.6%, while non-relapsed mortality ranged from 5.6% to 42%. The acute graft versus host disease (GvHD) incidence varied from 9.3% to 32%, while chronic GvHD rates ranged from 10% to 43%. Allo-HCT provides promising outcomes for patients aged 70 or older with transplant-eligible diseases. Disease progression, followed by infections, is the leading cause of mortality, underscoring the need for improved post-transplant care, including optimized GvHD regimens and strategies to reduce infection risk.
{"title":"Outcomes of Allogeneic Hematopoietic Stem Cell Transplantation in Patients Aged 70 Years and Older: A Systematic Review and Meta-Analysis","authors":"Moazzam Shahzad , Qamar Iqbal , Muhammad Kashif Amin , Amir Kasaiean , Iman Menbari Oskouie , Sarmad Zaman Warraich , James Yu , Iqra Anwar , Michael Jaglal , Muhammad Umair Mushtaq","doi":"10.1016/j.jtct.2024.12.022","DOIUrl":"10.1016/j.jtct.2024.12.022","url":null,"abstract":"<div><div>Allogeneic hematopoietic cell transplantation (allo-HCT) is a potential cure for many hematological malignancies. Historically, older adults were not considered eligible for allo-HCT due to increased toxicity and mortality concerns. This systematic review and meta-analysis aim to explore the outcomes of allo-HCT in patients aged 70 years or older. Following Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines, a comprehensive literature search was performed on PubMed, Cochrane Register of Controlled Trials, and Clinicaltrials.gov using MeSH terms and keywords for “Hematopoietic Stem Cell Transplantation” AND “Outcome Assessment” from the date of inception to June 30, 2024. Our search produced 102 articles. After excluding irrelevant and review articles during primary and secondary screening, eight original studies reporting outcomes of allo-HCT in patients aged 70 years or older were included. The survival data were retrieved from Kaplan–Meier (KM) curves using an online plot digitizer tool to calculate the overall survival (OS) and disease-free survival (DFS). The pooled KM curves were plotted and analyzed using the “MetaSurvival” package of R software version 4.2.1. Proportions and 95% confidence intervals (CIs) were extracted as well. A total of 2519 patients aged 70 years or older with allo-HCT were included in the analysis. The included patients’ age ranged from 70 to 84 years, and 68% were male. Median follow-up was 23.2 (0.4 to 122.5) months. The combined median OS was 14.84 months (95% CI: 11.61 to 19.50), with OS rates at 6, 12, 24, and 36 months of 71.8%, 54.5%, 41.9%, and 34.9%, respectively. The estimated pooled mean OS was 28.62 months (95% CI: 23.41 to 31.44). The pooled median DFS was 10.54 months (95% CI: 7.93 to 14.17), with DFS rates at 6, 12, 24, and 36 months of 61.5%, 47.5%, 37%, and 30.6%, respectively. The estimated pooled mean DFS was 24.45 months (95% CI: 18.30 to 23.74). The relapse rate ranged from 28% to 55.6%, while non-relapsed mortality ranged from 5.6% to 42%. The acute graft versus host disease (GvHD) incidence varied from 9.3% to 32%, while chronic GvHD rates ranged from 10% to 43%. Allo-HCT provides promising outcomes for patients aged 70 or older with transplant-eligible diseases. Disease progression, followed by infections, is the leading cause of mortality, underscoring the need for improved post-transplant care, including optimized GvHD regimens and strategies to reduce infection risk.</div></div>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"31 3","pages":"Pages 172.e1-172.e13"},"PeriodicalIF":3.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142928472","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-01DOI: 10.1016/j.jtct.2025.01.004
Effie W. Petersdorf , Caroline McKallor , Mari Malkki , Katherine Hsu , Meilun He , Stephen R. Spellman , Theodore Gooley , Philip Stevenson
Background
Recurrence of blood malignancy is the major cause of mortality after hematopoietic cell transplantation. NKG2 receptor/HLA-E ligand complexes play a fundamental role in the surveillance and elimination of transformed cells but their role in the control of leukemia in transplantation is unknown.
Objective
We tested the hypothesis that gene variation of patient and/or donor HLA-E ligand and donor NKG2C-NKG2A receptors are associated with the risks of relapse and mortality (primary endpoints) and GVHD and non-relapse mortality (secondary endpoints) after haploidentical transplantation.
Study Design
We retrospectively defined donor NKG2 receptor haplotypes and patient HLA-E ligands in 1629 haploidentical related transplantations. HLA-E residue 107 was genotyped in patients and donors. Single nucleotide polymorphisms descriptive of NKG2C and NKG2A haplotypes were characterized in donors. Overall mortality, relapse, nonrelapse mortality and chronic GVHD were studied using Cox regression models. Acute GVHD was studied by logistic regression.
Results
The hazard of relapse for patients transplanted from NKG2C-del/del donors was 51% lower than that from wt/wt donors (hazard ratio, HR, .49 [95% CI, .26 to .89) contributing to a HR for mortality of .62 (95% CI, .38 to 1.02). The HR of mortality among patients transplanted from a donor with 2 vs. 0 copies of the NKG2A rs35909400-rs2734440-rs12824474 CCC haplotype was HR 2.28 (95% CI, 1.34 to 3.86). The HRs of mortality for ArgArg and ArgGly patients compared to GlyGly patients were 1.42 (95% CI, 1.11 to 1.82) and 1.43 (95% CI, 1.13 to 1.81), respectively. Hazard ratios for nonrelapse mortality for patients with ArgGly or ArgArg genotypes compared to patients with GlyGly genotype were HR 1.60 (95% CI, 1.06 to 2.41) and HR 1.79 (95% CI, 1.21 to 2.66), respectively. Assessment of donor receptor/patient ligand pairings showed that among Arg-positive patients, the HR of mortality from donors with any wt-CCC/CCC haplotype was HR 2.52 (95% CI, 1.45 to 4.38) relative to donors with any wt-non CCC/CCC haplotype.
Conclusions
The success of haploidentical transplantation may be defined by the cumulative effects of donor NKG2 receptor and patient HLA-E ligand polymorphisms. Patient HLA-E ligand and donor NKG2C-NKG2A receptor haplotypes shed new light on their role in the control of malignancy.
{"title":"The Association of HLA-E Ligand and NKG2 Receptor Variation With Relapse and Mortality After Haploidentical Related Donor Transplantation","authors":"Effie W. Petersdorf , Caroline McKallor , Mari Malkki , Katherine Hsu , Meilun He , Stephen R. Spellman , Theodore Gooley , Philip Stevenson","doi":"10.1016/j.jtct.2025.01.004","DOIUrl":"10.1016/j.jtct.2025.01.004","url":null,"abstract":"<div><h3>Background</h3><div>Recurrence of blood malignancy is the major cause of mortality after hematopoietic cell transplantation. NKG2 receptor/HLA-E ligand complexes play a fundamental role in the surveillance and elimination of transformed cells but their role in the control of leukemia in transplantation is unknown.</div></div><div><h3>Objective</h3><div>We tested the hypothesis that gene variation of patient and/or donor HLA-E ligand and donor NKG2C-NKG2A receptors are associated with the risks of relapse and mortality (primary endpoints) and GVHD and non-relapse mortality (secondary endpoints) after haploidentical transplantation.</div></div><div><h3>Study Design</h3><div>We retrospectively defined donor NKG2 receptor haplotypes and patient HLA-E ligands in 1629 haploidentical related transplantations. HLA-E residue 107 was genotyped in patients and donors. Single nucleotide polymorphisms descriptive of NKG2C and NKG2A haplotypes were characterized in donors. Overall mortality, relapse, nonrelapse mortality and chronic GVHD were studied using Cox regression models. Acute GVHD was studied by logistic regression.</div></div><div><h3>Results</h3><div>The hazard of relapse for patients transplanted from NKG2C-del/del donors was 51% lower than that from wt/wt donors (hazard ratio, HR, .49 [95% CI, .26 to .89) contributing to a HR for mortality of .62 (95% CI, .38 to 1.02). The HR of mortality among patients transplanted from a donor with 2 vs. 0 copies of the NKG2A rs35909400-rs2734440-rs12824474 CCC haplotype was HR 2.28 (95% CI, 1.34 to 3.86). The HRs of mortality for ArgArg and ArgGly patients compared to GlyGly patients were 1.42 (95% CI, 1.11 to 1.82) and 1.43 (95% CI, 1.13 to 1.81), respectively. Hazard ratios for nonrelapse mortality for patients with ArgGly or ArgArg genotypes compared to patients with GlyGly genotype were HR 1.60 (95% CI, 1.06 to 2.41) and HR 1.79 (95% CI, 1.21 to 2.66), respectively. Assessment of donor receptor/patient ligand pairings showed that among Arg-positive patients, the HR of mortality from donors with any wt-CCC/CCC haplotype was HR 2.52 (95% CI, 1.45 to 4.38) relative to donors with any wt-non CCC/CCC haplotype.</div></div><div><h3>Conclusions</h3><div>The success of haploidentical transplantation may be defined by the cumulative effects of donor NKG2 receptor and patient HLA-E ligand polymorphisms. Patient HLA-E ligand and donor NKG2C-NKG2A receptor haplotypes shed new light on their role in the control of malignancy.</div></div>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"31 3","pages":"Pages 137-156"},"PeriodicalIF":3.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142972276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-01DOI: 10.1016/j.jtct.2025.01.881
Valentina Ardila , Hong Li , Claudio Brunstein , Matt Kalaycio , Ronald Sobecks , Craig S. Sauter , Betty K. Hamilton
Background
The relationship between obesity and graft-versus-host disease (GVHD) has been studied in both preclinical and clinical studies with varying results.
Objectives
We aimed to investigate the impact of obesity, as measured by body mass index (BMI), on the incidence, severity, and response to therapy of GVHD in a contemporary cohort.
Study Design
We conducted a retrospective study of patients undergoing allogeneic hematopoietic cell transplant (HCT) for acute myelogenous leukemia and myelodysplastic syndrome between January 2010 and December 2021 at the Cleveland Clinic. Incidence, grade, organ involvement, and response to therapy of acute and chronic GVHD were compared between patients with obesity (BMI ≥30) and without obesity. Secondary outcomes included relapse, nonrelapse mortality (NRM), and overall survival (OS).
Results
531 patients were identified, with a median follow-up of 19 months (range, 7-49). Mean (SD) BMI at time of HCT was 29.1 (6.3) kg/m2. There was no significant difference in demographic and HCT characteristics between patients with obesity (N = 199) and without obesity (N = 332). Development of any acute (42% versus 43%) or chronic (29% versus 30%) GVHD was similar in patients with and without obesity. Patients with obesity were less likely to have gastrointestinal involvement from chronic GVHD (28% versus 48%, P = .01). Skin (64% versus 56%), mouth (45% versus 35%) and eye (35% versus 27%) involvements were higher in patients with obesity, although statistically not significant. There were no significant differences in OS, NRM, or relapse.
Conclusion
There were no significant differences in incidence of GVHD among patients with and without obesity. Additional studies are needed to further understand potential differences in organ involvement.
{"title":"Impact of Obesity on GVHD in Patients Undergoing Allogeneic Hematopoietic Cell Transplant for Hematologic Malignancies","authors":"Valentina Ardila , Hong Li , Claudio Brunstein , Matt Kalaycio , Ronald Sobecks , Craig S. Sauter , Betty K. Hamilton","doi":"10.1016/j.jtct.2025.01.881","DOIUrl":"10.1016/j.jtct.2025.01.881","url":null,"abstract":"<div><h3>Background</h3><div>The relationship between obesity and graft-versus-host disease (GVHD) has been studied in both preclinical and clinical studies with varying results.</div></div><div><h3>Objectives</h3><div>We aimed to investigate the impact of obesity, as measured by body mass index (BMI), on the incidence, severity, and response to therapy of GVHD in a contemporary cohort.</div></div><div><h3>Study Design</h3><div>We conducted a retrospective study of patients undergoing allogeneic hematopoietic cell transplant (HCT) for acute myelogenous leukemia and myelodysplastic syndrome between January 2010 and December 2021 at the Cleveland Clinic. Incidence, grade, organ involvement, and response to therapy of acute and chronic GVHD were compared between patients with obesity (BMI ≥30) and without obesity. Secondary outcomes included relapse, nonrelapse mortality (NRM), and overall survival (OS).</div></div><div><h3>Results</h3><div>531 patients were identified, with a median follow-up of 19 months (range, 7-49). Mean (SD) BMI at time of HCT was 29.1 (6.3) kg/m<sup>2</sup>. There was no significant difference in demographic and HCT characteristics between patients with obesity (N = 199) and without obesity (N = 332). Development of any acute (42% versus 43%) or chronic (29% versus 30%) GVHD was similar in patients with and without obesity. Patients with obesity were less likely to have gastrointestinal involvement from chronic GVHD (28% versus 48%, <em>P</em> = .01). Skin (64% versus 56%), mouth (45% versus 35%) and eye (35% versus 27%) involvements were higher in patients with obesity, although statistically not significant. There were no significant differences in OS, NRM, or relapse.</div></div><div><h3>Conclusion</h3><div>There were no significant differences in incidence of GVHD among patients with and without obesity. Additional studies are needed to further understand potential differences in organ involvement.</div></div>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"31 3","pages":"Pages 178.e1-178.e9"},"PeriodicalIF":3.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143012383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-01DOI: 10.1016/S2666-6367(25)01028-0
{"title":"Officers and Directors of ASTCT","authors":"","doi":"10.1016/S2666-6367(25)01028-0","DOIUrl":"10.1016/S2666-6367(25)01028-0","url":null,"abstract":"","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"31 3","pages":"Page A3"},"PeriodicalIF":3.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143511131","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-01DOI: 10.1016/j.jtct.2024.11.015
Amanda Kirane , David Lee , Charlotte Ariyan
Adoptive T cell therapy (ACT) using tumor-infiltrating lymphocytes (TILs) is a promising personalized immunotherapy approach, spearheaded by Dr. Steven Rosenberg, targeting various cancer types. Despite initial challenges in TIL production, recent advancements have showcased its superiority to immune checkpoint blockade in metastatic melanoma, even after anti-PD-1 therapy failure. The expedited manufacturing process, now around 3 weeks, coupled with the US Food and Drug Administration approval of lifileucel in 2024, is poised to propel TIL therapy into mainstream oncology. This commentary delves into the critical surgical aspects of TIL harvesting, emphasizing the integral role of surgeons in ensuring optimal TIL quality, safety, and therapeutic effectiveness. By shedding light on these considerations, this article aims to guide and enhance collaborative efforts in advancing TIL therapy for patients facing limited treatment options.
{"title":"Surgical Considerations in Tumor-Infiltrating Lymphocyte Therapy: Challenges and Opportunities","authors":"Amanda Kirane , David Lee , Charlotte Ariyan","doi":"10.1016/j.jtct.2024.11.015","DOIUrl":"10.1016/j.jtct.2024.11.015","url":null,"abstract":"<div><div>Adoptive T cell therapy (ACT) using tumor-infiltrating lymphocytes (TILs) is a promising personalized immunotherapy approach, spearheaded by Dr. Steven Rosenberg, targeting various cancer types. Despite initial challenges in TIL production, recent advancements have showcased its superiority to immune checkpoint blockade in metastatic melanoma, even after anti-PD-1 therapy failure. The expedited manufacturing process, now around 3 weeks, coupled with the US Food and Drug Administration approval of lifileucel in 2024, is poised to propel TIL therapy into mainstream oncology. This commentary delves into the critical surgical aspects of TIL harvesting, emphasizing the integral role of surgeons in ensuring optimal TIL quality, safety, and therapeutic effectiveness. By shedding light on these considerations, this article aims to guide and enhance collaborative efforts in advancing TIL therapy for patients facing limited treatment options.</div></div>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"31 3","pages":"Pages S591-S598"},"PeriodicalIF":3.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143610672","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-01DOI: 10.1016/j.jtct.2024.11.013
James W. Smithy , Adam J. Schoenfeld , Allison Betof Warner
The recent approval of lifileucel by the US Food and Drug Administration in February 2024 was the culmination of over 3 decades of research in adoptive cell therapy with tumor-infiltrating lymphocytes (TILs) for unresectable melanoma. In this review, we highlight key historical data for TIL therapy in melanoma as well as ongoing efforts to improve its efficacy and applicability.
{"title":"The Clinical TIL Experience in Melanoma: Past, Present, Future","authors":"James W. Smithy , Adam J. Schoenfeld , Allison Betof Warner","doi":"10.1016/j.jtct.2024.11.013","DOIUrl":"10.1016/j.jtct.2024.11.013","url":null,"abstract":"<div><div>The recent approval of lifileucel by the US Food and Drug Administration in February 2024 was the culmination of over 3 decades of research in adoptive cell therapy with tumor-infiltrating lymphocytes (TILs) for unresectable melanoma. In this review, we highlight key historical data for TIL therapy in melanoma as well as ongoing efforts to improve its efficacy and applicability.</div></div>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"31 3","pages":"Pages S626-S634"},"PeriodicalIF":3.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143610677","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
We previously reported that the area under the curve of log-transformed cytomegalovirus antigenemia (CMV-AUC) until 100 days after allogeneic hematopoietic cell transplantation (allo-HCT) was associated with an increased risk of non-relapse mortality. We applied a risk-adapted letermovir (LTV) prophylaxis strategy guided by a risk score that predicts a higher CMV-AUC. First, we retrospectively analyzed 278 allo-HCT recipients between 2007 and 2017 (Period 1). We scored risk factors for higher CMV-AUC by odds ratios: malignant lymphoma including adult T cell leukemia/lymphoma (1 point), an unrelated or haploidentical donor (1 point), and recipient/donor CMV serostatus (+/+; 2 points, +/-; 3 points). We have administered LTV to patients with a total score of ≥ 4 points. We then focused on 143 patients who underwent allo-HCT when we applied this strategy (Period 2). Forty patients (28%) in Period 2 received LTV prophylaxis. Two patients (5.4%) exhibited higher CMV-AUC among 37 patients in the higher-risk group (≥ 4 points). However, as many as 33% of the patients with 3 points in Period 2 experienced higher CMV-AUC. Notably, in the lower-risk patients of Period 2, 68% of patients who received systemic steroids for acute graft-versus-host-disease (GVHD) developed higher CMV-AUC. Our risk-adapted LTV prophylaxis strategy effectively prevented higher CMV-AUC in the higher-risk group and reduced the use of LTV. Additionally, including the use of systemic steroids for acute GVHD in this risk-adapted approach is preferable.
{"title":"Risk-Adapted Letermovir Prophylaxis Based on a Scoring System Predicting a Higher Burden of Cytomegalovirus Exposure After Allogeneic Hematopoietic Cell Transplantation","authors":"Shunto Kawamura , Shin-ichiro Fujiwara , Shun-ichi Kimura , Junko Takeshita , Hideki Nakasone , Kazuki Yoshimura , Yuya Nakata , Takuto Ishikawa , Akari Matsuoka , Tomohiro Meno , Yuhei Nakamura , Masakatsu Kawamura , Nozomu Yoshino , Yukiko Misaki , Ayumi Gomyo , Machiko Kusuda , Rui Murahashi , Kento Umino , Daisuke Minakata , Masahiro Ashizawa , Yoshinobu Kanda","doi":"10.1016/j.jtct.2025.01.883","DOIUrl":"10.1016/j.jtct.2025.01.883","url":null,"abstract":"<div><div>We previously reported that the area under the curve of log-transformed cytomegalovirus antigenemia (CMV-AUC) until 100 days after allogeneic hematopoietic cell transplantation (allo-HCT) was associated with an increased risk of non-relapse mortality. We applied a risk-adapted letermovir (LTV) prophylaxis strategy guided by a risk score that predicts a higher CMV-AUC. First, we retrospectively analyzed 278 allo-HCT recipients between 2007 and 2017 (Period 1). We scored risk factors for higher CMV-AUC by odds ratios: malignant lymphoma including adult T cell leukemia/lymphoma (1 point), an unrelated or haploidentical donor (1 point), and recipient/donor CMV serostatus (+/+; 2 points, +/-; 3 points). We have administered LTV to patients with a total score of ≥ 4 points. We then focused on 143 patients who underwent allo-HCT when we applied this strategy (Period 2). Forty patients (28%) in Period 2 received LTV prophylaxis. Two patients (5.4%) exhibited higher CMV-AUC among 37 patients in the higher-risk group (≥ 4 points). However, as many as 33% of the patients with 3 points in Period 2 experienced higher CMV-AUC. Notably, in the lower-risk patients of Period 2, 68% of patients who received systemic steroids for acute graft-versus-host-disease (GVHD) developed higher CMV-AUC. Our risk-adapted LTV prophylaxis strategy effectively prevented higher CMV-AUC in the higher-risk group and reduced the use of LTV. Additionally, including the use of systemic steroids for acute GVHD in this risk-adapted approach is preferable.</div></div>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"31 3","pages":"Pages 184.e1-184.e11"},"PeriodicalIF":3.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143012405","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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